The overall goal of this proposal is to elucidate the cellular mechanisms involved in immunomodulation of tumor growth in a mouse model system. Studies have been designed to analyze the cellular interactions and receptor specificities of effector (Te) and suppressor T cells (Ts) reactive against methylcholanthrene-induced tumors in the syngeneic host. T effector cells in these systems belong to the Lyt-1+ subset. Determination of the heterogeneity of these cells for shared, unique, or virus-related tumor-associated antigens will proceed by the development of a series of cloned Te cell lines. Clones will be analyzed for specificity in vitro through use of proliferation assay, and for efficiency in conferring protection against tumor growth in vivo. The requirements for Te recognition of native versus macrophage processed tumor antigen will also be examined and the relevant antigen presenting cell will be phenotyped. Effector and suppressor T cells active in this tumor system have also been shown to recognize determinants expressed on certain allogeneic normal cells. Experiments are proposed to identify the relevant alloantigen and to determine the mechanism by which this cross-reactivity between tumor and H-2 antigens occurs to provide further information on the biological relationship between these cell surface structures. Further definition of the tumor-specific suppressor network, which involves both cells and cell-derived factors, will focus on the role of idiotype-anti-interactions as a means of cellular activation. Ts induced as a result of anti-I-A antibody administration in vivo will be characterized with respect to their position in this network. This system will be used as a means to describe the mechanism of action of heterologous and monoclonal anti-I-A antibodies in modulating both Te and Ts responses in vivo and in vitro. Based upon this analysis of the interralationships between positive (effector) and negative (suppressor) pathways in tumor immunity, strategies for immunotherapy will be developed by combining the adoptive transfer of cloned effector lines with treatments designed to eliminate suppressive activity. Through this approach it should be possible to manipulate the relative activities or participating T cell subsets by immunologically specific means and alter the balance of immune reactivity to the host's advantage.